Hipotireoidismo

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Thyroid consensus
Arq Bras Endocrinol Metab. 2013;57/3
The Brazilian consensus for the 
clinical approach and treatment of 
subclinical hypothyroidism in adults: 
recommendations of the thyroid 
Department of the Brazilian Society 
of Endocrinology and Metabolism
Consenso brasileiro para a abordagem clínica e 
tratamento do hipotireoidismo subclínico em adultos: 
recomendações do Departamento de Tireoide da 
Sociedade Brasileira de Endocrinologia e Metabologia
Jose A. Sgarbi1, Patrícia F. S. Teixeira2, Lea M. Z. Maciel3, Glaucia M. F. S. 
Mazeto4, Mario Vaisman2, Renan M. Montenegro Junior5, Laura S. Ward6
ABSTRACT
Introduction: Subclinical hypothyroidism (SCH), defined as elevated concentrations of thyroid 
stimulating hormone (TSH) despite normal levels of thyroid hormones, is highly prevalent in 
Brazil, especially among women and the elderly. Although an increasing number of studies 
have related SCH to an increased risk of coronary artery disease and mortality, there have been 
no randomized clinical trials verifying the benefit of levothyroxine treatment in reducing these 
risks, and the treatment remains controversial. Objective: This consensus, sponsored by the 
Thyroid Department of the Brazilian Society of Endocrinology and Metabolism and developed 
by Brazilian experts with extensive clinical experience with thyroid diseases, presents these 
recommendations based on evidence for the clinical management of SCH patients in Brazil. 
Materials and methods: After structuring the clinical questions, the search for evidence in the 
literature was initially performed in the MedLine-PubMed database and later in the Embase 
and SciELO – Lilacs databases. The strength of evidence was evaluated according to the Oxford 
classification system and established based on the experimental design used, considering the 
best available evidence for each question and the Brazilian experience. Results: The topics 
covered included SCH definition and diagnosis, natural history, clinical significance, treatment 
and pregnancy, and the consensus issued 29 recommendations for the clinical management 
of adult patients with SCH. Conclusion: Treatment with levothyroxine was recommended for 
all patients with persistent SCH with serum TSH values ≥ 10 mU/L and for certain patient sub-
groups. Arq Bras Endocrinol Metab. 2013;57(3):166-83
Keywords
Hypothyroidism; subclinical hypothyroidism; consensus; guidelines
1 Disciplina de Endocrinologia 
e Metabologia, Faculdade 
de Medicina de Marília 
(Famema), Marília, SP, Brazil
2 Serviço de Endocrinologia, 
Departamento de Clínica 
Médica, Universidade Federal 
do Rio de Janeiro (UFRJ), 
Rio de Janeiro, RJ, Brazil
3 Departamento de Clínica 
Médica, Faculdade de Medicina 
de Ribeirão Preto, Universidade 
de São Paulo (FMRP-USP), 
Ribeirão Preto, SP, Brazil
4 Disciplina de Endocrinologia 
e Metabologia, Departamento 
de Clínica Médica, Faculdade 
de Medicina de Botucatu, 
Universidade Estadual Paulista 
(FMB-Unesp), Botucatu, SP, Brazil
5 Universidade Federal do Ceará 
(UFC), Fortaleza, CE, Brazil
6 Laboratório de Genética 
Molecular do Câncer, Faculdade 
de Ciências Médicas, Universidade 
Estadual de Campinas (FCM-
Unicamp), Campinas, SP, Brazil
Correspondence to: 
José A. Sgarbi
Disciplina de Endocrinologia e 
Metabologia, Faculdade de Medicina 
de Marília 
Av. Tiradentes, 1310
17519-000 – Marília, SP, Brazil
jasgarbi@famema.br
Received on Mar/5/2013
Accepted on Mar/5/2013
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167Arq Bras Endocrinol Metab. 2013;57/3
 Subclinical hypothyroidism
RESUMO
Introdução: O hipotireoidismo subclínico (HSC), definido por concentrações elevadas do TSH 
em face de níveis normais dos hormônios tireoidianos, tem elevada prevalência no Brasil, par-
ticularmente entre mulheres e idosos. Embora um número crescente de estudos venha asso-
ciando o HSC com maior risco de doença arterial coronariana e de mortalidade, não há ensaio 
clínico randomizado sobre o benefício do tratamento com levotiroxina na redução dos riscos e 
o tratamento permanece controverso. Objetivo: Este consenso, patrocinado pelo Departamen-
to de Tireoide da Sociedade Brasileira de Endocrinologia e Metabologia e desenvolvido por 
especialistas brasileiros com vasta experiência clínica em tireoide, apresenta recomendações 
baseadas em evidências para uma abordagem clínica do paciente com HSC no Brasil. Materiais 
e métodos: Após estruturação das questões clínicas, a busca das evidências disponíveis na 
literatura foi realizada inicialmente na base de dados do Medline-PubMed e posteriormente nas 
bases Embase e SciELO – Lilacs. A força da evidência, avaliada pelo sistema de classificação de 
Oxford, foi estabelecida a partir do desenho de estudo utilizado, considerando-se a melhor evi-
dência disponível para cada questão e a experiência brasileira. Resultados: Os temas aborda-
dos foram definição e diagnóstico, história natural, significado clínico, tratamento e gestação, 
que resultaram em 29 recomendações para a abordagem clínica do paciente adulto com HSC. 
Conclusão: O tratamento com levotiroxina foi recomendado para todos os pacientes com HSC 
persistente com níveis séricos do TSH ≥ 10 mU/L e para alguns subgrupos especiais de pacien-
tes. Arq Bras Endocrinol Metab. 2013;57(3):166-83
Descritores
Hipotiroidismo; hipotiroidismo subclínico; consenso; diretriz
INTRODUCTION
S ubclinical hypothyroidism (SCH) has been bio-chemically defined by the presence of elevated se-
rum thyroid stimulating hormone (TSH) levels despite 
normal serum concentrations of thyroid hormones 
(1-3). The prevalence of SCH in the general popula-
tion is approximately 4%-10%, being higher in women 
and the elderly and inversely proportional to the iodine 
content in the diet (4-7). In Brazil, the prevalence of 
elevated TSH in a representative sample of 1,220 adult 
women of Rio de Janeiro city was 12.3% and reached 
19.1% among women who were over 70 years of age 
(8). In the metropolitan area of São Paulo, the preva-
lence of hypothyroidism in 1,085 individuals was 8% 
(9). Among 1,110 individuals from a Japanese-Bra-
zilian population of Bauru ≥ 30 years old, the preva-
lence of hypothyroidism was 11.1% in females and 8.7% 
in males (10), and in an elderly population of São Paulo 
city, the prevalence of SCH was 6.5% and 6.1% for fe-
males and males, respectively (11).
In the last decade, a growing number of studies 
have associated SCH with increased risk of coronary 
artery disease and mortality (12,13). However, strong 
and conclusive evidence has not been found from ran-
domized prospective double-blind studies for the po-
tential benefits of levothyroxine therapy.
Recently, the American Thyroid Association in 
conjunction with the American Association of Clinical 
Endocrinologists published recommendations (14) for 
hypothyroidism; however, there were few specific re-
commendations for the subclinical dysfunction. In Bra-
zil, there is currently no consensus on SCH diagnosis 
and treatment.
The present consensus unifies the efforts of the 
Thyroid Department of the Brazilian Society of En-
docrinology and Metabolism to develop recommenda-
tions based on available evidence in the literature with 
the clinical approach to SCH patients in our country. 
The main objectives were to develop recommendations 
to assist clinicians in delivering the best health care pos-
sible to patients and avoid unnecessary procedures wi-
thin the context of the Brazilian health care system.
METHODS 
This consensus follows the strategic policy of the 
Thyroid Department of the Brazilian Society of En-
docrinology and Metabolism in the development of 
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168 Arq Bras Endocrinol Metab. 2013;57/3
 Subclinical hypothyroidism
national consensus for major thyroid diseases, directed 
at this population and in the context of the Brazilian 
health care system.
The model used was based on the Guidelines Pro-
gram (15) of the Brazilian Medical Association (Associa-
ção Médica Brasileira, AMB) and the Federal Council of 
Medicine (Conselho Federal de Medicina, CFM) because 
this program represents a genuinely national initiative 
and is already known by the medical and academic com-
munity in the country. After choosing the participants 
with recognized academic performance and extensive cli-
nical experience with thyroid diseases, the clinical ques-
tions were developed. The publications were obtained 
by searching the Medline-PubMed, Embase and SciE-
LO – Lilacs databases. The keywords were identified by 
different means such as accessing the “Citation” (Pub-
Med) after obtaining known publications that provided 
answers to the specified questions. The Oxford classifica-
tion was used to classify the degree of recommendation 
or the strength of evidence of the work (Table 1) (15); 
this classification establishes the strength of the evidence 
based on the experimental design used, considering both 
the best available evidence for each question and the 
Brazilian experience. This system was chosen primarily 
because it is the same used by the Guidelines Program 
of AMB/CFM (16), with which the Brazilian medical 
community and academia are familiar. 
What is the normal TSH value in the general popula-
tion according to age and in specific populations?
The reference limits for TSH, similar to any other 
test, are obtained by averaging the TSH values from a 
supposedly healthy population without thyroid disea-
se within a 95% confidence interval (between the 2.5 
and 97.5 percentiles) (17). Ideally, normal TSH levels 
should be based on values determined from fasting 
samples collected in the morning, from individuals wi-
thout a personal history or a family history of thyroid 
disorders, without goiter, without thyroid disorders ob-
served on the ultrasound and with negative anti-thyro-
peroxidase (TPOAb) and anti-thyroglobulin (TgAb) 
antibodies (18). However, it is difficult to obtain this 
ideal population, and the reference limits commonly 
used today for all races, genders and ethnicities were 
provided by large North-American population studies, 
which defined the reference limit of serum TSH for a 
normal adult to be between 0.4 and 4.5 mU/L (4,19).
A statistical reanalysis of the North-American popu-
lation data, considered the effects of age, race/ethnicity, 
gender and body weight in individuals who had neither 
thyroid disease nor goiter; were not taking medication; 
were not pregnant; were not taking estrogens, andro-
gens or lithium; had normal urinary concentrations of 
iodine; and in whom antithyroid antibodies were unde-
tectable. This reanalysis showed that the mean normal 
TSH values are between 1.40 and 1.90 mU/L and are 
1.0 mU/L higher in the White population than in the 
Black population (19). Table 2 shows the mean levels 
and the 2.5 and 97.5 percentiles obtained by the analy-
sis of 13,296 individuals of different ages without appa-
rent thyroid disease (19).
Table 1. Definition of the strength of recommendation of the evidence 
according to the Oxford classification (modified from references 15 and 
16) 
Recommendation Strength of evidence
A Experimental and observational studies of best 
consistency
B Experimental and observational studies of less 
consistency
C Case reports (uncontrolled studies)
D Opinion without critical evaluation, based on 
consensus, physiological studies or animal models
Table 2. The distribution of average and 2.5 and 97.5 percentiles of the 
TSH values obtained from 13.296 individuals of all races and both sexes. 
who were thyroid disease free (modified from reference 19)
Age (years) 2.5 Percentile Median 97.5 Percentile
All ages 0.42 1.40 4.30
13-19 0.41 1.30 3.78
20-29 0.40 1.30 3.60
30-39 0.38 1.25 3.60
40-49 0.44 1.40 3.90
50-59 0.49 1.50 4.20
60-69 0.46 1.66 4.70
70-79 0.47 1.74 5.60
80 + 0.44 1.90 6.30
TSH values expressed in mU/L.
DEFINITION AND DIAGNOSTIC
What is the definition of SCH?
Recommendation 1
Although the subclinical term is associated with the ab-
sence of obvious symptoms of hormone production failure 
by the thyroid gland, SCH is defined biochemically by ele-
vated serum TSH values in the presence of normal serum 
free T4 (FT4) (1,2) (D).
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169Arq Bras Endocrinol Metab. 2013;57/3
A national study was performed on 960 adults be-
tween 18 and 60 years of age (excluding pregnant wo-
men), without goiter or detectable antithyroid antibo-
dies, who did not use drugs that potentially interfere 
with thyroid function or status, had no personal or fa-
mily history of thyroid disorders and had normal levels 
of serum FT4. In this study, the mean TSH value was 
1.52 mU/L, with a 2.5 percentile value of 0.43 mU/L 
and a 97.5 percentile value of 3.24 mU/L (20).
The effect of age on the upper limit of what is con-
sidered normal should always be considered, especially 
when the treatment with levothyroxine is debated for 
elderly individuals in whom the physiological increase 
of serum TSH may represent a cardiovascular protecti-
ve factor (21) and may be associated with greater lon-
gevity (22).
The reference limits in the pediatric population are 
higher shortly after birth, decreasing quickly over the 
first days and then progressively with increasing age 
(23,24). Table 3 shows the percentiles obtained in a 
population of 654 boys and girls aged up to 18 years 
of age (23).
ce ranges for each population, particularly in regions 
where there may be iodine deficiency. In the absence of 
local standards, the upper limits of normal TSH values 
can be up to 2.5 mU/L in the first trimester and up to 
3.5 mU/L in the following two trimesters, as descri-
bed in studies with a large number of pregnant women 
(27,28).
Recommendation 2
The reference value for serum TSH for healthy adults is 
between 0.4 and 4.5 mU/L (4,19) (A). For pediatric 
(23) (B) and elderly patients (22) (B), it is important 
to evaluate the values according to the normal ranges su-
ggested for each age. During pregnancy, TSH values up 
to 2.5 mU/L in the first trimester and 3.5 mU/L in the 
following two trimesters should be considered the normal 
upper limits in the absence of a local laboratory reference 
(27) (B).
How should SCH be diagnosed?
In general, a laboratory investigation for thyroid 
dysfunction is performed in individuals with a clinical 
suspicion of a thyroid disorder. SCH can be associa-
ted with symptoms of hypothyroidism (5); however, 
the clinical manifestations are not usually evident, and 
when they occur, they may be rather non-specific. Thus, 
an investigation should be performed when there is a 
suspicion of SCH or as a screening in individuals from 
specific groups such as women over 35 years of age 
every 5 years, patients with previous personal or family 
history of thyroid disease, undergoing thyroid surgery, 
previous therapy with radioiodine or external radiation 
in the neck, type 1 diabetes, personal or family history 
of autoimmune disease, Down and Turner syndromes, 
lithium or amiodarone treatment, depression, dyslipi-
demia and hyperprolactinemia (1,14).
The diagnosis of SCH is biochemical and consists 
of the detection of elevated serum concentrations of 
TSH despite normal levels of FT4, when other causes 
of high TSH are excluded (Table 4) (2,17). Althoughan exact and absolute upper cutoff level of TSH cannot 
be defined (28), TSH values between 4.5 mU/L and 
20 mU/L have been accepted as the cutoff (4,19) and 
upper level (13), respectively, for the SCH diagnosis.
SCH must also be differentiated from other cau-
ses (Table 4) of elevated TSH with normal serum FT4 
concentrations such as the following: the physiological 
elevation of TSH with increasing age (29); use of re-
combinant TSH in patients undergoing cancer thyroid 
Table 3. The reference percentiles of TSH in children (modified from 
reference 23)
Age
Percentile
2,5 25 50 75 97,5
7 days 0,32 1,66 3,11 5,30 12,27
14 days 0,34 1,64 3,01 5,06 11,44
21 days 0,35 1,61 2,89 4,76 10,43
28 days 0,36 1,58 2,80 4,55 9,75
3 months 0,32 1,78 3,25 5,32 11,21
1 year 0,38 1,55 2,62 4,10 8,14
4 years 0,66 1,52 2,18 3,02 5,15
7 years 0,80 1,69 2,35 3,19 5,24
12 years 0,66 1,48 2,11 2,90 4,88
18 years 0,49 1,22 1,79 2,51 3,38
TSH values expressed in mU/L.
During pregnancy, there is a decrease in serum TSH 
values (25). However, the complexity and dynamics of 
the hormonal changes occurring during pregnancy, es-
pecially in the first trimester, make the establishment 
of reference values more difficult. Changes in iodine 
metabolism, the production of chorionic gonadotro-
pin (beta-hCG), increases in thyroid hormone carrier 
proteins, changes in excretion and elevation of thyroid 
hormones levels per se, alter the reference values (26). 
Thus, it is important that laboratories establish referen-
 Subclinical hypothyroidism
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170 Arq Bras Endocrinol Metab. 2013;57/3
surgery (30); untreated primary adrenal insufficiency 
(31); cross-reaction of TSH with heterophilic antibo-
dies against rat proteins (32); and mutations in the 
TSH receptor (33). In most cases, a careful patient his-
tory helps the clinician establish the correct diagnosis.
Recommendation 3 
SCH is biochemically diagnosed by serum TSH ≥ 4.5 
mU/L despite normal FT4 levels (4,19) (A), when other 
causes of high TSH are excluded. The consensus accepts 
values up to 20 mU/L as the upper limit for TSH in the 
diagnosis of SCH (13) (D).
Recommendation 4 
The determination of serum TSH should be requested in 
situations where there is clinical suspicion of SCH (5) (A) 
or as a screening in specific groups of high-risk individuals 
(1) (D).
How should persistent and progressive SCH be diffe-
rentiated from transitional SCH?
Only patients with persistent SCH should be con-
sidered for treatment. Thus, persistent SCH should be 
differentiated from the situations associated with tem-
porary increases in TSH (Table 4) including recovery 
from subacute thyroiditis (34), after administration of 
radioiodine to treat Graves’ disease (35) and during re-
covery from debilitating diseases (36).
A significant proportion of patients with SCH show 
normal TSH levels during the first 2-5 years of follow-
-up (37), especially those with serum TSH value ≤ 10 
mU/L (38). Thus, when there is a suspicion of SCH, 
the determination of TSH should be repeated after 3-6 
months to exclude laboratory error or temporary cau-
ses of TSH elevation.
Recommendation 5
Persistent or progressive SCH must be differentiated from 
temporary causes of high TSH, which may regress during 
follow-up (37) (A) especially in patients with serum TSH 
≤ 10 mU/L (38) (B). TSH should be repeated initially 
within 3 months to confirm persistent SCH (1) (D).
How should SCH be classified according to TSH levels?
SCH has been classified according to the magnitu-
de of the increase in serum TSH concentrations, the 
risk of progression to overt hypothyroidism and the as-
sociation with comorbidities. Serum TSH values ≥ 10 
mU/L are associated with a high risk of progression to 
overt hypothyroidism (39), coronary artery disease and 
death (13). Thus, some authors have proposed the sub-
-classification of SCH according to severity into mild-
-moderate SCH (TSH values 4.5-9.9 mU/L) or severe 
SCH (TSH values ≥ 10 mU/L) (2).
Recommendation 6
Considering the rates of progression to overt hypothyroi-
dism (39) (B) and the risk of coronary events and morta-
lity (13) (A), SCH should be classified according to serum 
TSH concentrations into mild-moderate (TSH values 
4.5-9.9 mU/L) and severe (TSH values ≥ 10 mU/L) (2) 
(D).
NATURAL HISTORY 
What are the predictors of progression to overt hypothyroi-
dism?
SCH may progress to overt hypothyroidism, re-
main relatively stable for long periods or regress to a 
normal thyroid function depending on individual and 
population characteristics (40). In the Whickham study 
(7), women with elevated TSH levels (> 6 mU/L) and 
positive antithyroid antibodies had an annual rate of 
progression to overt hypothyroidism of 4.3%, while for 
women with high levels of TSH and negative thyroid 
antibodies, this rate was only 2.6%. In at least one other 
longitudinal study, the combination of elevated TSH 
and positive antithyroid antibodies was predictive of 
progression to overt hypothyroidism in females (41). 
Table 4. Causes of increases in serum TSH concentrations despite normal 
FT4, that should be differentiated from SCH
Causes 
Temporary increase in TSH
Recent adjustments in the dose of levothyroxine
Hypothyroidism under-treated with levothyroxine
Recovery from subacute thyroiditis
After administration of radioiodine for Graves’ disease
Recovery phase from Graves’ disease
Other causes of TSH elevation 
TSH elevation with increasing age
Use of recombinant TSH in patients undergoing thyroid cancer surgery 
Untreated primary adrenal insufficiency 
Cross-reaction of TSH with heterophilic antibodies against rat proteins
Mutations in the TSH receptor
 Subclinical hypothyroidism
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Prospective studies in a cohort of patients showed hi-
gher rates of progression that were generally also as-
sociated with serum TSH concentrations and the pre-
sence of thyroid autoimmunity. Diez and Iglesias (39) 
observed that patients with SCH and TSH levels < 10 
mU/L had a lower incidence rate (1.76%) of overt hy-
pothyroidism compared with patients with TSH levels 
ranging from 10 to 14.9 mU/L (19.7%) and 15 to 19.9 
mU/L (73.5%). Huber and cols. (42) showed that the 
annual incidence of overt hypothyroidism ranged from 
3.3% (TSH values 6-12 mU/L) to 11.4% (TSH values 
> 12 mU/L) and also depended on the presence of 
positive antithyroid antibodies. In Brazil, Rosario and 
cols. (43) showed that not only the presence of TPOAb 
antibodies but also ultrasonographic aspects indicating 
autoimmune thyroiditis are associated with an increa-
sed risk of progression to overt hypothyroidism. Simi-
larly, Marcocci and cols. (44) concluded that patients 
with autoimmune thyroiditis and hypoechogenicity 
on thyroid ultrasound were more likely to progress to 
overt hypothyroidism. Increased iodine intake was also 
a risk factor for progression in a Chinese population 
study (45).
Conversely, in a significant proportion of patients, 
elevated serum TSH levels observed in the first eva-
luation might progress to normal levels in a second 
evaluation. In a large Israeli population study (37), the 
normalization rate was 62% in 5 years of follow-up; 
therefore, it is imperative to repeat TSH measurements 
before making treatment decisions. The return to eu-
thyroidism tends to be more frequent in patients with 
serum TSH levels 4-6 mU/L, while TSH values bet-
ween 10-15 mU/L are associated with a low frequency 
of thyroid function normalization (38,39,46,47).
The majority of elderlypatients with SCH remain 
in this condition after 12 (76.7%) (38) and 24 mon-
ths (56%) (48), and TSH values ≥ 10 mU/L was an 
independent predictor of risk for progression to overt 
hypothyroidism (39,48). 
Children and adolescents appear to have low risk 
of SCH progression to overt hypothyroidism (49,50). 
In a prospective study, most patients (88%) experien-
ced normalization or stabilization of their TSH levels 
(49). The presence of goiter, celiac disease, positive 
antithyroid antibodies, higher TSH levels in the ini-
tial presentation or progressive elevation of TSH levels 
appear to be predictors of overt hypothyroidism in this 
age group (51,52).
Recommendation 7
In females (7,39) (B), serum TSH levels (39) (B), thyroid 
autoimmunity (7,39,41) (B), and increased iodine in-
take (45) (A) are risk factors associated with progression 
to overt hypothyroidism. TSH levels ≥ 10 mU/L are as-
sociated with an increased risk of progression to overt 
hypothyroidism in adults (38,39,41,42) (B) and in the 
elderly (48) (A). There is no evidence of risk in males, 
possibly because of the low prevalence of hypothyroidism 
among men.
Recommendation 8
The risk of progression to overt hypothyroidism is low 
among children and adolescents (49,50) (B), but it may 
be higher in the presence of goiter, celiac disease, positi-
ve antithyroid antibodies and higher TSH levels (51,52) 
(B).
Recommendation 9
The determination of TPOAb antibodies (7,39,41) (B) 
and a thyroid ultrasound (43,44) (A,B) may be useful 
in determining SCH etiology and predicting the risk of 
progression to overt hypothyroidism.
CLINICAL SIGNIFICANCE
Does SCH affect quality of life and neurocognitive func-
tion?
The effects of overt hypothyroidism on patient qua-
lity of life are well established but remain controversial 
in SCH patients. Only 24% of patients with SCH were 
classified as having overt hypothyroidism in a study ai-
med at developing a clinical index based on scores to 
assess the severity of hypothyroidism (53). In a cross-
-sectional study conducted in Colorado (USA) (5), 
SCH patients reported more symptoms of hypothyroi-
dism compared with euthyroid controls; however, the 
sensitivity and the positive predictive value were low. In 
a study of an Australian community (54), SCH was not 
associated with a worsening of the quality of life, which 
is a result similar to the one obtained in Brazil (55). In 
specific elderly populations (56-58), SCH was not asso-
ciated with significant effects on cognition, depression 
and anxiety.
In Brazil, the results obtained from cross-sectional 
studies have been controversial. Almeida and cols. (59) 
did not find differences in the neurocognitive evalu-
ation between 65 patients with SCH and 31 healthy 
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172 Arq Bras Endocrinol Metab. 2013;57/3
controls. The same group found in another study that, 
although symptoms of depression and anxiety were 
positively associated with TSH levels in SCH patients, 
levothyroxine replacement did not have any benefits 
(60).
Recommendation 10 
SCH can be symptomatic in a small proportion of pa-
tients (5,53) (A,B); however, there is no overwhelming 
evidence regarding the effects of this disorder on quality 
of life and cognitive function (54) (A). In the elderly, 
SCH is not associated with effects on cognitive function, 
depression or anxiety (56-58) (A,B,A).
Is there an association between dyslipidemia and 
SCH?
Thyroid hormones act in different pathways of lipid 
metabolism, and overt hypothyroidism may be associa-
ted with dyslipidemia through different mechanisms 
(61). It has been hypothesized that these changes may 
occur in patients with SCH, but the results of different 
studies are conflicting. In the Rotterdam study (62), no 
significant differences were found in serum total cho-
lesterol levels and non-HDL cholesterol (triglycerides 
and LDL-c were not assessed) between individuals with 
SCH and those with euthyroidism, although a strong 
association of SCH with the risk of atherosclerosis and 
myocardial infarction in elderly women was observed. 
The data obtained from the study National Health and 
Nutritional Examination Survey (NHANES) (63) in 
the North American population have reinforced the-
se findings because no evidence of an association bet-
ween SCH and dyslipidemia was found. Likewise, no 
association of SCH with lipid profile abnormalities was 
found in a Japanese-Brazilian population (10). In a 
large cross-sectional study (64) with 7,000 consecuti-
ve outpatients, there was no association of SCH with 
changes in serum total cholesterol levels, LDL-c and 
triglycerides.
Moreover, other population studies found an asso-
ciation between SCH and dyslipidemia. In the Health, 
Aging, and Body Composition Study (65), there was 
a significant association between SCH and increased 
serum total cholesterol levels, but only among Black 
women. In the Australian study conducted in Bussel-
ton (66), elevated serum LDL-c levels were associated 
with SCH even after adjusting for sex and age. In the 
Tromso study (67), a positive correlation between se-
rum TSH levels and lipid parameters was also found. 
The study performed in Colorado (USA) (5) with more 
than 25,000 participants (2,336 with SCH) showed a 
significant association of SCH with high serum total 
cholesterol levels and a positive correlation between 
serum TSH levels and total cholesterol; however, the 
analyses were not adjusted for age and sex. More recen-
tly, an association of SCH with dyslipidemia was shown 
in a Chinese population (68). Factors that appear to 
contribute and strengthen the association of SCH with 
dyslipidemia include TSH levels > 10 mU/L (69,70), 
a smoking habit (71) and insulin resistance (72,73). 
Moreover, population studies involving euthyroid in-
dividuals suggest that small elevations in serum TSH, 
even within the normal range, may be associated with 
elevated lipid parameters (74,75).
Recommendation 11
There is a discrepancy among the population studies re-
garding a potential association of SCH with dyslipide-
mia; however, serum TSH levels > 10 mU/L (69,70) (A), 
a smoking habit (71) (B) and insulin resistance (72,73) 
(B) are associated with an increased risk for dyslipidemia 
in SCH patients.
What are the effects of SCH on the vascular endothe-
lium?
Thyroid hormones exert effects on the endothelium 
and vascular smooth muscle cells, which in turn, play a 
major role in the modulation of vascular tone (76). In 
addition, the TSH receptor is expressed in the vascular 
smooth muscle cells (77), and TSH has direct effects 
on human endothelial cells (78,79).
Lekakis and cols. (80) were the first to describe a 
negative relationship between SCH and endothelium-
-dependent vasodilation, measuring the brachial artery 
flow-mediated dilation that was subsequently confir-
med by other studies (81,82). In a randomized dou-
ble-blind crossover study, Razvi and cols. (83) showed 
that replacement therapy with levothyroxine increased 
the flow-mediated dilatation of the brachial artery in 
SCH patients. More recently, Traub-Weidinger and 
cols. (84) observed a reversible coronary microvascular 
dysfunction after treatment with levothyroxine in 10 
patients with SCH due to autoimmune disease.
Recommendation 12
There are few studies in the literature regarding the 
effects of SCH on the vascular endothelium. The majority 
of studies have a sample with an insufficient number of 
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patients, thereby limiting the strength ofthe evidence re-
garding the cause-effect relationship.
What are the effects of SCH on cardiac function?
Thyroid hormones have important effects on car-
diac physiology through genetic and non-genetic me-
chanisms, and it has been speculated that changes in 
these mechanisms as a result of SCH could be associa-
ted with changes in the cardiac structure and function 
as occurs in overt hypothyroidism (76).
Changes in systolic and diastolic functions have 
been reported in patients with SCH in small studies 
with methodological limitations (85-91), while no 
structural or functional alterations were associated with 
SCH in 2 population studies (92,93).
Conversely, the association of SCH with heart fai-
lure has been demonstrated more consistently in epi-
demiological studies and meta-analyses, especially for 
serum TSH levels > 10 mU/L (94-97) and in the 
elderly (94,95,97). However, in a single cohort with 
repeated measurements of thyroid function over time, 
the association of persistent SCH with heart failure in 
elderly patients was not confirmed, suggesting that the 
temporary SCH effects could mask those from the per-
sistent SCH in studies based only in one determination 
of thyroid function (98).
Recommendation 13
There is no consistent evidence regarding the effects of 
SCH on cardiac structure and systolic and diastolic func-
tions in population studies (92,93) (B,A).
Recommendation 14
There is evidence showing a significant association of 
SCH with congestive heart failure, especially in the elder-
ly (94,95,97) (A) and in patients with TSH levels above 
10 mU/L (96) (A).
Is SCH associated with cardiovascular risk and mor-
tality?
Several prospective population studies (10,12,62,94-
107) have explored the potential associations of SCH 
with cardiovascular risk and mortality; however, the 
results are conflicting, possibly due to multiple factors 
including the following: differences in the definitions 
used for SCH and coronary artery disease; inclusion of 
populations with specific characteristics, with different 
ethnicities and ages; different inclusion and exclusion 
criteria; and different adjustments of the confounding 
factors that interfere with the prognosis, among others 
(108).
In Brazil, in one prospective population study in the 
Japanese-Brazilian community of Bauru (10), SCH was 
significantly associated with an increased risk of death 
from any cause in 7.5 years of follow up, but not with 
cardiovascular causes. However, the number of events 
was small, which most likely limited the statistical po-
wer to determine significance. Moreover, because it was 
a specific population of Japanese-Brazilians, the data 
cannot be generalized for the entire Brazilian popula-
tion. 
The impact of SCH on cardiovascular risk has also 
been investigated in different meta-analyses (109-112), 
but the results were also conflicting, possibly because 
of the heterogeneity of the studies. However, more re-
cently, a complex meta-analysis (13) based on indivi-
dual data from 11 prospective studies included 55,287 
subjects with homogeneous criteria for inclusion and 
exclusion and a single definition for SCH and coronary 
artery disease. In this study (13), SCH was significantly 
associated with both increased risk and death from co-
ronary artery disease. The risks for both outcomes were 
higher for TSH levels ≥ 10 mU/L, but death as a result 
of coronary artery disease was also significant with TSH 
levels ≥ 7 mU/L.
In the elderly, however, a meta-analysis (21) did not 
find any association of SCH with cardiovascular risk 
and mortality, suggesting that the SCH does not exert 
the same effect on cardiovascular risk in the elderly 
compared to a younger population.
Recommendation 15
There is consistent evidence for an association of SCH 
with risk of coronary artery disease and death from coro-
nary artery disease, especially for TSH values ≥ 10 mU/L 
(13) (A), but this is not observed in elderly patients aged 
> 65 years (21) (A).
TREATMENT
When should SCH be treated?
The risk of progression to overt hypothyroidism is 
the first parameter to consider in the clinical decision 
regarding treatment. Therefore, patients with persistent 
SCH, especially with serum TSH levels ≥ 10 mU/L 
(38,39,41,42), positive TPOAb (7,39,41) and/or with 
ultrasonographic changes (44) that suggest thyroid au-
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toimmunity would be candidates for treatment because 
of the characteristics associated with a higher rate of 
progression to overt hypothyroidism.
The presence of symptoms related to hypothyroi-
dism is often considered by clinicians to indicate the 
treatment. However, the effects of replacement thera-
py with levothyroxine in patients with SCH on mood, 
cognition and quality of life vary among the different 
studies according to the type of population, with the 
definition of SCH and methods of measuring outco-
me. There are few clinical, randomized and placebo-
-controlled trials that have evaluated the impact of 
treatment on these outcomes. Some trials have de-
monstrated beneficial effects (113-116), while others 
did not confirm these results (117-120). In the elderly 
with SCH, a randomized study showed that treatment 
with levothyroxine does not improve cognitive func-
tion compared with a placebo (120), although only 27 
of the 42 placebo-treated patients completed the study, 
which may have influenced the results.
Another possible benefit of levothyroxine treatment 
in patients with SCH would be in regard to dyslipi-
demia. However, few randomized placebo-controlled 
trials have evaluated the effect of levothyroxine on the 
lipid profile of SCH patients. Some trials did not obser-
ve a reduction in the levels of lipid parameters with the 
treatment (113-115,118), while others demonstrated 
favorable effects (67,83,121-123). Two meta-analyses 
also assessed the effects of levothyroxine replacement 
on the lipid profile of SCH patients (69,70). The first 
meta-analysis (69) was favorable to treatment, but most 
of the selected studies were not randomized. Converse-
ly, in the second meta-analysis (70), which selected only 
placebo-controlled randomized studies, the beneficial 
effects of levothyroxine were slight and only affected 
total cholesterol. Both meta-analyses (69,70) showed 
that the potential benefits of the treatment occurred 
in patients with TSH levels > 10 mU/L. Later, a few 
randomized trials have been published with the same 
goal, but all presented with methodological limitations. 
In a randomized crossover study, Ravzi and cols. (83) 
observed the beneficial effects of levothyroxine treat-
ment on total cholesterol LDL, but without differences 
compared with the placebo group, and at the end of 3 
months, only 71/100 patients had TSH levels within 
the target range. 
In a study of paired analysis (pre and post interven-
tion), Adrees and cols. (124) demonstrated favorable 
effects of levothyroxine treatment on women with 
SCH, and in a randomized placebo-controlled trial con-
ducted in Brazil, Teixeira and cols. (125) demonstrated 
that the levothyroxine replacement reduced the levels 
of LDL-c and total cholesterol, especially in postmeno-
pausal women with positive antithyroid antibodies and 
serum TSH levels > 8.0 mU/L. However, only 38 of 
the 60 subjects completed the 6 months of treatment.
There are also few randomized placebo-controlled 
trials that demonstrated a beneficial effect of SCH tre-
atment on endothelial function (83,122) (A) or cardiac 
structure and function, and the studies had methodolo-
gical limitations and conflicting results (83,87,88,126-
129).
However, there is consistentevidence (13) for an 
association of SCH with increased risk and death from 
coronary artery disease, especially for TSH levels above 
10 mU/L. Death as a result of coronary arterial disea-
se was also significantly higher for TSH values from 7 
mU/L. In a meta-analysis (21), the association of SCH 
with increased cardiovascular risk and mortality was sig-
nificant only for individuals aged less than 65 years. Des-
pite these data on the association of risk between SCH 
and cardiovascular outcomes and death, no randomi-
zed placebo-controlled clinical trials have been conduc-
ted to evaluate the impact of levothyroxine treatment 
on these outcomes in patients with SCH. However, 
there is indirect evidence of potential benefits obtained 
from population-based cohort studies data to assess 
these outcomes, where one group of SCH patients was 
treated and another was not. In the Cardiovascular He-
alth Study cohort, individuals with SCH treated with 
levothyroxine had a lower risk of cardiovascular events 
compared with untreated individuals (97). A reanalysis 
of the Whickham study (12) demonstrated that the tre-
atment of SCH was associated with a reduction in total 
mortality after 20 years of follow up, even after multiple 
adjustments for other factors that influence prognosis. 
In the study Preventive Cardiology Information Sys-
tem (PreCIS; Cleveland Clinic – USA) (106), patients 
with moderate SCH (TSH > 6.0-10 mU/L) and overt 
hypothyroidism had a higher risk of mortality from all 
causes, especially in indivi duals under 65 years that did 
not receive levothyroxine throughout the cohort. Fi-
nally, in a UK cohort (130), young adult patients (40-
70 years old) recently diagnosed with SCH (TSH, 5.01 
to 10 mU/L) that had received levothyroxine treat-
ment were less likely to have coronary artery disease 
events and less likely to die as a result of all causes at 7.6 
years of follow-up compared with patients who did not 
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receive levothyroxine. However, no positive effect was 
observed in the elderly subjects (> 70 years old).
Recommendation 16
SCH treatment remains controversial, and it is not su-
pported by evidence because of the lack of randomized 
and placebo-controlled studies with sufficient numbers of 
patients to demonstrate the benefits of the treatment on 
cardiovascular risk and mortality risk. Thus, treatment 
should be considered in specific situations, depending on 
the available evidence regarding the clinical significance 
of SCH, in subgroups of patients who might benefit from 
treatment and based on individual clinical judgment 
(D).
Recommendation 17
Treatment for SCH should only be considered for patients 
with persistent SCH and after confirmation of serum 
TSH levels after 3 - 6 months (37) (A).
Recommendation 18 
The consensus recommends levothyroxine treatment for 
all patients with persistent SCH and serum concentra-
tions of TSH ≥ 10 mU/L (Table 5) because of the higher 
risk of progression to overt hypothyroidism (39,41,42) 
(B), heart failure (96) (A), coronary artery disease and 
mortality (13) (A). There are also cohort studies with 
indirect evidence showing the benefits of SCH treatment 
on cardiovascular risk and mortality (12,97,106,130) 
(B). Furthermore, there is evidence (70) (A) suggesting 
a favorable effect of levothyroxine treatment on serum to-
tal cholesterol in patients with SCH and TSH levels > 10 
mU/L.
Recommendation 19 
For patients with persistent SCH and serum TSH levels < 
10 mU/L (Table 5), treatment may be considered for sub-
groups of patients with specific characteristics, as follows:
Female patients (7,39) (B) with positive TPOAb 
(7,39,41) (B) and/or with ultrasound changes that su-
ggest Hashimoto’s thyroiditis (43,44) (A,B) and with a 
progressive increase in serum TSH levels due to the higher 
risk of progression to overt hypothyroidism.
Patients with preexisting cardiovascular disease or 
high cardiovascular risk (e.g., metabolic syndrome, dys-
lipidemia, diabetes, arterial hypertension), especially pa-
tients aged < 65 years (21) (A) and with TSH levels > 7 
mU/L (13) (A), due to the higher cardiovascular risk 
and death from cardiovascular disease.
The consensus did not find evidence to support the 
recommendation of levothyroxine treatment in patients 
with SCH to relieve symptoms or improve quality of life 
and cognitive function. However, dependent on indi-
vidual clinical judgment, the consensus agrees with the 
previous recommendation (1) (D) of performing a thera-
peutic test with levothyroxine for a short period of time. If 
the clinical manifestations remain unchanged after nor-
malization of TSH, the treatment should be discontinued.
When should elderly patients with SCH be treated?
Large population studies did not demonstrate an 
association of SCH with cognitive dysfunction, anxiety 
or depression in patients older than 65 years (56-58), 
and a randomized placebo-controlled trial (120) did 
not find any benefit of levothyroxine treatment repla-
cement on the cognitive function of patients > 65 years 
and with SCH. 
Evidence from population-based cohort studies 
(94,95,97) associates SCH with an increased risk of 
heart failure in elderly patients with TSH levels > 10 
mU/L. However, in a recent study of a population-
-based cohort with determinations of thyroid function 
over time, the association of SCH with persistent heart 
failure in elderly patients has not been confirmed (98). 
Furthermore, there has been no study on the potential 
benefits of the SCH treatment in elderly on the heart 
failure risk.
Table 5. Recommendations (R) for the treatment of persistent subclinical hypothyroidism 
Parameter TSH (> 4.5 < 10 mU/L) TSH (≥ 10 mU/L)
Age ≤ 65 years
Without comorbidities (R18) No Yes
Risk of progression to overt hypothyroidism (R 19A) Consider to treat Yes
Preexisting cardiovascular disease or cardiovascular risk (R 19-B) Consider to treat if TSH ≥ 7 mU/L Yes
Hypothyroidism symptoms (R 19-C) Therapeutic test should be considered Yes
Age > 65 years (R 20, R 21) No Yes
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It is postulated that mild-moderate SCH (TSH le-
vels > 4.5 and ≤ 10 mU/L) in the elderly may be asso-
ciated with benefits, either as a protective factor against 
cardiovascular risk and mortality (21,22,99) or by de-
monstrations that such patients have better physical 
function and gait speed as shown by a 2-year follow-up 
study of patients aged 70-79 years (131). Furthermore, 
population-based cohort studies (97,106,130) showed 
that although the SCH treatment has a favorable effect 
on the reduction of cardiovascular risk and/or mortali-
ty in young adults, the same was not observed in elderly 
patients.
Recommendation 20
SCH treatment in elderly patients > 65 years is recom-
mended only when TSH levels > 10 mU/L are sustained 
(Table 5) due to a lack of association with cardiovascular 
risk and mortality in this age group (21) (A), the lack of 
favorable effects of the treatment in population-based co-
hort studies (106,130) (B) and because of the higher risk 
of heart failure in elderly patients with SCH and TSH 
levels > 10 mU/L (94,95,97) (A).
Recommendation 21 
There is no recommendation for treatment for elderly 
(> 65 years old) SCH patients to relieve symptoms and 
improve quality of life (120) (A).
What are the treatment risks?
It is estimated that a significant proportion of pa-
tients undergoing levothyroxine replacement may be 
using supraphysiological doses resultingin subclinical 
or overt hyperthyroidism. In a study performed in Co-
lorado (USA) (5), approximately 40% of the patients 
with hypothyroidism were treated with supraphysio-
logical doses of levothyroxine, while in Brazil (132), 
a recent multicenter study showed that this situation 
occurred in approximately 14.4% of patients. The indu-
ced subclinical hyperthyroidism in these cases is asso-
ciated with an increased risk of atrial fibrillation (133), 
especially in the elderly over 65 years of age (134), and 
reduced bone mass in postmenopausal women (135).
Recommendation 22
The risks of SCH treatment are inherent to the use of 
high doses of levothyroxine, with special clinical relevance 
in the elderly due to increased risk of atrial fibrillation 
(133,134) (A) and in postmenopausal women due to the 
risk of osteoporosis (135) (B).
SUBCLINICAL HYPOTHYROIDISM IN PREGNANCY
How is SCH diagnosed during pregnancy? 
The diagnosis of SCH during pregnancy results 
from laboratory findings characterized by high concen-
trations of TSH despite normal levels of FT4 for the 
gestational age (136).
There is strong evidence that the reference range for 
TSH is lower during pregnancy (17,18) compared with 
the normal reference range in non-pregnant women 
(approximately 0.45 to 4.5 mU/L). A larger decrease 
in TSH levels is observed in the first trimester, and it 
is temporary, depending on the beta-hCG concentra-
tions, which can stimulate the TSH receptor. The TSH 
concentrations rise gradually in subsequent trimesters. 
The reference values of TSH during pregnancy (me-
dian and 2.5% and 97.5% percentiles) obtained from 
several studies (25,28,137) are shown in table 6.
The best methods for the FT4 determination du-
ring pregnancy are tandem mass spectrometry, liquid 
chromatography and equilibrium dialysis. The usual 
methods of FT4 measurement are influenced by the 
increase in the thyroxine-binding globulin (TBG) and 
the decrease in albumin concentrations that occur du-
ring pregnancy. These changes may influence FT4 im-
munoassays, which can also occur for the total T4 and 
the FT4 index (138). Caution in interpreting their va-
lues and establishing the normal range for each trimes-
ter by laboratories is recommended (139).
Table 6. References values of TSH (mU/L) in the different trimesters of pregnancy
Study
Trimesters of pregnancy
First Second Third
Stricker and cols. 1.04 (0.09-2.83) 1.02 (0.2-2.79) 1.14 (0.31-2.9)
Soldin and cols. 0.98 (0.24-2.99) 1.09 (0.46-2.95) 1.2 (0.43-2.78)
Bocos-Terraz and cols. 0.92 (0.03-2.65) 1.12 (0.12-2.64) 1.29 (0.23-3.56)
Values expressed as median and percentiles (2.5-97.5%).
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Recommendation 23
Reference values for TSH should be determined for each 
trimester of pregnancy by the local laboratory. If these 
values are not available, the following reference values 
should be used: first trimester, 0.1-2.5 mU/L; second 
trimester, 0.2-3.5 mU/L; and third trimester, 0.3-3.5 
mU/L (27) (B).
Recommendation 24
If the best methods to measure FT4 are not available, clini-
cians should use the usual methods for its determination. 
However, clinicians should be aware of the limitations of 
these methods and of the reference values according to the 
method used (138,139) (B).
Recommendation 25 
For the diagnosis of SCH in the first trimester of preg-
nancy, TSH values ranging between 2.5 to 10 mU/L as-
sociated with FT4 values within the normal range for the 
gestational age should be considered (136) (D).
Does SCH increase maternal risk?
Most studies in pregnant women with SCH that 
analyzed complications during pregnancy suggest that 
the SCH is associated with adverse effects during preg-
nancy. Fetal loss was the most frequently associated 
obstetric complication. Benhadi and cols. (140) found 
a positive linear relationship between fetal loss and in-
creased TSH concentrations. Negro and cols. (141) 
found an increased rate of fetal loss in women with 
negative TPOAb and TSH values between 2.5 to 5.0 
mU/L compared with those who had TSH values < 
2.5 mU/L. Allan and cols. (142) also observed that 
women with elevated TSH levels (> 6 mU/L) had a 
higher percentage of fetal death compared with con-
trols. Other complications associated with SCH were 
gestational hypertension or preeclampsia, preterm de-
livery, low birth weight, placental abruption and pos-
tpartum hemorrhage (143). However, in a cohort of 
10,990 pregnant women (144), SCH detected in the 
first and second trimesters was not associated with ad-
verse effects.
Recommendation 26
Although retrospective, several studies (142,143) (B) 
have suggested that SCH is associated with higher risk 
of pregnancy complications. Only 2 prospective studies 
(140,141) (B) have suggested that the treat ment of preg-
nant women reduces the risk of these complications, but 
these studies require confirmation by other randomized 
studies.
Does SCH increase fetal risk?
Thyroid hormones are essential for brain develop-
ment, and their deficiencies can cause deficits in neuro-
nal differentiation and migration, axonal and dendritic 
growth, myelin formation and synaptogenesis (145).
However, the deleterious effects of SCH on fetal 
neurocognitive development are still unknown. Two 
studies have shown that low concentrations of thyroid 
hormones in the early stages of pregnancy were associa-
ted with decreased intelligence quotient (IQ) in chil-
dren tested at 10 months and 7 years (146,147).
A large study (Controlled Antenatal Thyroid Study; 
CATS) performed in England (148) evaluated preg-
nant women until the 16th week of gestation. Those 
with TSH levels above the 97.5% percentile and/or 
FT4 levels below the 2.5% percentile were treated or 
not treated with levothyroxine. The results showed no 
difference in the IQ of the children evaluated at 3 years 
of age between the 2 groups. However, this study eva-
luated only children at 3 years of age, which may have 
limited the significance of the findings because of the 
technical difficulty of assessing IQ in this age group. 
Moreover, the percentage of children with an IQ < 85 
was higher in the group of pregnant women with SCH 
that were not treated compared to the treated group.
Recommendation 27
There is little evidence suggesting potential deleterious 
effects of SCH on fetal neurocognitive development 
(146,147) (B,C), and there is no evidence of benefit from 
the levothyroxine treatment in pregnant women with 
SCH (148) (A).
Should we screen SCH during pregnancy?
There is controversy regarding the universal scree-
ning for hypothyroidism in all pregnant women. The 
consequences for the mother and fetus are well establi-
shed when overt hypothyroidism is not diagnosed and 
treated during pregnancy. However, these consequen-
ces are not defined for SCH because there is only one 
randomized prospective study evaluating the effects of 
levothyroxine treatment and subsequent child develo-
pment (148). Thus, the American College of Obste-
tricians and Gynecologists (149) does not recommend 
the universal screening of pregnant women, but only 
for those women at high risk for thyroid dysfunction. 
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Recently, the American Thyroid Association (136) also 
stated that there is not enough evidence to recommend 
or not recommend universal screening of TSH in preg-
nant women in the first trimester.
In one study (150) comparing the detection of 
thyroid dysfunction through the universal screening 
ofpregnant women with the active search approach in 
high-risk pregnancies noted that 30% of pregnant wo-
men with thyroid dysfunction were not detected with 
the latter approach.
The pregnant women at high risk for developing 
thyroid dysfunction present with one of the following 
conditions: 1) history of hyperthyroidism or hypo-
thyroidism or previous postpartum thyroiditis; 2) his-
tory of cervical irradiation; 3) goiter; 4) family history 
of thyroid disease; 5) positive antithyroid antibody; 6) 
type 1 diabetes mellitus or other autoimmune disea-
se; 7) history of miscarriages or premature births; 8) 
symptoms and signs of thyroid dysfunction including 
anemia, high cholesterol and hyponatremia; and 9) tre-
atment with amiodarone (150).
Recommendation 28 
There is insufficient evidence to recommend or not recom-
mend universal screening for hypothyroidism with TSH 
in pregnant women in the first trimester of gestation, but 
the consensus agrees with the recommendation of an ac-
tive search in pregnant women at high risk for thyroid 
dysfunction (136,149-151) (D,D,B,B).
When and how should SCH be treated during preg-
nancy?
Most retrospective studies (142,143) suggest an 
association of SCH with adverse effects during preg-
nancy, but there are no prospective randomized stu-
dies on the potential benefits of SCH treatment during 
pregnancy. However, it is known that levothyroxine 
treatment during pregnancy is safe when used carefully.
Once started, the doses of levothyroxine should be 
lower than those prescribed for overt hypothyroidism 
treatment. The concentrations of TSH and FT4 should 
be measured 4 weeks after the beginning of the treat-
ment (151) and monthly until the middle of pregnancy 
and at least in the 26th and 32nd weeks of gestation 
(149). The goal is to maintain concentrations of TSH 
lower than 2.5 mU/L in the first trimester of preg-
nancy or 3.5 mU/L in the second and third trimesters 
(27). 
Recommendation 29
There is no consistent evidence to recommend for or 
against SCH treatment during pregnancy. However, this 
consensus accepts that the treatment should be initiated 
at the time of diagnosis due to retrospective studies sug-
gesting adverse effects during pregnancy and low risk of 
treatment (142,143) (B).
Acknowledgments: we are grateful to Dr. Nathalia Carvalho de 
Andrada by reviewing the degree of recommendations and the 
strength of evidence.
Disclosure: no potential conflict of interest relevant to this article 
was reported.
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